Yeast oxysterol-binding proteins: sterol transporters or regulators of cell polarization?
Yeast oxysterol-binding proteins: sterol transporters or regulators of cell polarization?
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DOI：
10.1007/s11010-008-9999-7
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发表时间：
2009-06-01
影响因子：
4.3
通讯作者：
Menon, Anant K.
中科院分区：
文献类型：
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作者：
Beh, Christopher T.;Alfaro, Gabriel;Menon, Anant K.
氧甾醇结合蛋白（OSBP）和OSBP相关蛋白（ORPs）是一个保守的可溶性细胞质蛋白家族，可以结合甾醇，在膜间区室之间转运，并影响甾醇运输。这些特性使orp成为脂质转移蛋白（LTPs）的有吸引力的候选者，后者直接介导非囊性固醇向质膜的转移。为了测试酵母orp （Osh蛋白）是否为甾醇ltp，我们研究了缺乏一种、几种或全部Osh蛋白的Osh缺失突变体的内质网（ER）到质膜（PM）固醇转运。在条件OSH突变体中，ER-PM麦角甾醇的转运速度比表达完整的OSH蛋白的细胞慢了20倍。尽管这一初步发现表明奥什蛋白起着固醇ltp的作用，但情况要复杂得多。Osh蛋白已在Rho小GTPase信号传导中发挥作用。Osh蛋白增强细胞极化，它们特别影响参与极化细胞生长的蛋白的定位，如septin和GTPases Cdc42p、Rho1p和Sec4p。此外，极化分泌到膜生长部位的特定途径需要Osh蛋白，这表明这就是Osh蛋白影响Cdc42p-和rho1p依赖性极化的方式。我们的研究结果表明，Osh蛋白将固醇运输和固醇依赖的细胞信号传导与细胞极化控制结合起来。
Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) are a conserved family of soluble cytoplasmic proteins that can bind sterols, translocate between membrane compartments, and affect sterol trafficking. These properties make ORPs attractive candidates for lipid transfer proteins (LTPs) that directly mediate nonvesicular sterol transfer to the plasma membrane. To test whether yeast ORPs (the Osh proteins) are sterol LTPs, we studied endoplasmic reticulum (ER)-to-plasma membrane (PM) sterol transport in OSH deletion mutants lacking one, several, or all Osh proteins. In conditional OSH mutants, ER-PM ergosterol transport slowed similar to 20-fold compared with cells expressing a full complement of Osh proteins. Although this initial finding suggested that Osh proteins act as sterol LTPs, the situation is far more complex. Osh proteins have established roles in Rho small GTPase signaling. Osh proteins reinforce cell polarization and they specifically affect the localization of proteins involved in polarized cell growth such as septins, and the GTPases Cdc42p, Rho1p, and Sec4p. In addition, Osh proteins are required for a specific pathway of polarized secretion to sites of membrane growth, suggesting that this is how Osh proteins affect Cdc42p- and Rho1p-dependent polarization. Our findings suggest that Osh proteins integrate sterol trafficking and sterol-dependent cell signaling with the control of cell polarization.